Projects
Gene editing for cystic fibrosis - tackling the translatability hurdle KU Leuven
This project is focussed on novel gene editing modalities and delivery methods to develop a gene therapy treatment for the monogenetic disease cystic fibrosis which primarily manifests with lung disease. Objectives: (1) To use gene editing (in particular base and prime editing) for efficient correction of CFTR (gene mutations in CFTR are responsible for cystic fibrosis) in primary human organoid and airway models. (2) To develop safe and ...
A gene editing strategy for refractory CFTR mutations causing cystic fibrosis. KU Leuven
The goal of our project is to develop CRISPR-Cas gene editing therapy for CFTR mutations refractory to current CFTR modulators. A functional rescue will be assessed in human CF intestinal organoïds and airway cultures.
Targeted editing of the PSIP1 gene encoding LEDGF/p75 protects cells against HIV infection KU Leuven
Gene therapy has long held promise to correct a variety of human diseases. Discovery of the Clustered Regularly-Interspaced Short Palindromic Repeats (CRISPR), the mechanism of the CRISPR-based prokaryotic adaptive immune system (CRISPR-associated system, Cas) and its repurposing into a potent gene editing tool has revolutionized the field of molecular biology and generated excitement for new and improved gene therapies. Additionally, the ...
RNA Based Gene Therapy In A Model Of RNA Based Gene Therapy In A Model Of Usher syndrome KU Leuven
Usher syndrome (USH) is the most prevalent cause of combined deafness and blindness in humans. USH is categorized in three distinct subtypes based on severity of hearing loss and presence of vestibular dysfunction. The hearing loss due to mutations in different USH genes results from disorganization of the hair bundles of the cochlear hair cells. In all three USH subtypes visual impairment is due to retinitis pigmentosa (RP). Mutations in ...
An integrated CRISPR/iPSC-based approach to elucidate uncertain variation in RPE65, a target for gene therapy Ghent University
In 2017 and 2018, Luxturna received FDA and EMA approval as the first gene therapy product to treat patients with biallelic RPE65-mutations, causing severe inherited blindness. Eligibility for gene therapy requires a complete molecular diagnosis, which is often hampered by the identification of variants of uncertain significance (VUS). To this end, we first will set up a biochemical assay to assess the pathogenicity of coding RPE65 VUS, by ...
The GEne Therapy INnovation Training Network KU Leuven
Gene therapy has transitioned from a distant hope to reality. To date 3 rAAV gene therapies are approved in the EU, >30 phase III clinical trials ongoing, and exciting developments in therapeutic gene editing in the pipeline. However, fundamental limitations in the bioprocessing of gene therapy vectors limit broader application. Manufacturing is not automated, with an open process environment, limited scalability and robustness, and ...
Study of kidney progenitor cells and potential of gene therapy in nephropathic cystinosis. KU Leuven
In this proposal we focus on nephropathic cystinosis as a monogenetic disease affecting kidney glomeruli and proximal tubules. With no curative treatment available, renal replacement therapy is the only option. Cystinosis is characterized by lysosomal cystine accumulation due to mutations in the CTNS gene encoding the protein cystinosin. Over the last few years the cystinotic research field reached a scientific consensus which states that ...
Genome editing strategies to restore altered splicing events KU Leuven
Cystic fibrosis is an autosomal recessive disease caused by mutations in the CFTR gene. A significant number of mutations (~13%) alter the correct splicing of the CFTR gene, causing the transcription of aberrant transcripts resulting in the production of a non-functional CFTR channel. We focus our research on two intronic CF causing mutations, 3272-26A>G and 3849+10kbC>T that create a new acceptor and donor splice ...
Gene therapeutic intervention during ex vivo lung perfusion as a platform to modulate human lung disease KU Leuven
Lung transplantation (LTx) is the ultimate therapy to treat patients suffering from for end-stage lung disease. Unfortunately, LTx is accompanied by a low survival rate. Primary Graft Dysfunction (PGD) is a severe form of acute lung injury after LTx that is a major cause of poor survival. Although much progress has been made in understanding the risks and mechanisms of PGD, there is still no effective treatment. Ex-vivo lung perfusion (EVLP) ...